Optimizing dual energy cone beam CT protocols for preclinical imaging and radiation research

Objective: The aim of this work was to investigate whether quantitative dual-energy CT (DECT) imaging is feasible for small animal irradiators with an integrated cone-beam CT (CBCT) system. Methods: The optimal imaging protocols were determined by analyzing different energy combinations and dose levels. The influence of beam hardening effects and the performance of a beam hardening correction (BHC) were investigated. In addition, two systems from different manufacturers were compared in terms of errors in the extracted effective atomic numbers (Z(eff)) and relative electron densities (rho(e)) for phantom inserts with known elemental compositions and relative electron densities. Results: The optimal energy combination was determined to be 50 and 90kVp. For this combination, Z(eff) and r rho(e) can be extracted with a mean error of 0.11 and 0.010, respectively, at a dose level of 60cGy. Conclusion: Quantitative DECT imaging is feasible for small animal irradiators with an integrated CBCT system. To obtain the best results, optimizing the imaging protocols is required. Well-separated X-ray spectra and a sufficient dose level should be used to minimize the error and noise for Z(eff) and rho(e). When no BHC is applied in the image reconstruction, the size of the calibration phantom should match the size of the imaged object to limit the influence of beam hardening effects. No significant differences in Z(eff) and rho(e) errors are observed between the two systems from different manufacturers. Advances in knowledge: This is the first study that investigates quantitative DECT imaging for small animal irradiators with an integrated CBCT system

Investigation of the recombination of the retarded shell of "born-again" CSPNe by time-dependent radiative transfer models

A standard planetary nebula stays more than 10 000 years in the state of a photoionized nebula. As long as the timescales of the most important ionizing processes are much smaller, the ionization state can be characterized by a static photoionization model and simulated with codes like CLOUDY (Ferland et al. 1998). When the star exhibits a late Helium flash, however, its ionizing flux stops within a very short period. The star then re-appears from itsopaque shell after a few years (or centuries) as a cold giant star without any hard ionizing photons. Describing the physics of such behavior requires a fully time-dependent radiative transfer model. Pollacco (1999), Kerber et al. (1999) and Lechner & Kimeswenger (2004) used data of the old nebulae around V605 Aql and V4334 Sgr to derive a model of the pre-outburst state of the CSPN in a static model. Their argument was the long recombination time scale for such thin media. With regard to these models Schoenberner (2008) critically raised the question whether a significant change in the ionization state (and thus the spectrum) has to be expected after a time of up to 80 years, and whether static models are applicable at all.Comment: (3 pages, 1 figure, to appear in proceedings of the IAU Symposium 283: "Planetary Nebulae: An Eye to the Future", Eds.: A. Manchado, L. Stanghellini and D. Schoenberner; presenting author: Stefan Kimeswenger

A novel data management platform to improve image-guided precision preclinical biological research

Objective: Preclinical biological research is mandatory for developing new drugs to investigate the toxicity and efficacy of the drug. In this paper, the focus is on radiobiological research as an example of advanced preclinical biological research. In radiobiology, recent technological advances have produced novel research platforms which can precisely irradiate targets in animals and use advanced onboard image-guidance, mimicking the clinical radiotherapy environment. These platforms greatly facilitate complex research combining several agents simultaneously (in our example, radiation and non-radiation agents). Since these modern platform can produce a large amount of wide-ranging data, one of the main impediments in preclinical research platforms is a proper data management system for preclinical studies. Methods: A preclinical data management system, inspired by current radiotherapy clinical data management systems was designed. The system was designed with InterSystems technology, i.e. a programmable Enterprise Service Bus solution. New DICOM animal imaging standards are used such as DICOM suppl. 187 for storing small animal acquisition context and the DICOM second generation course model. Results: A small animal big data warehouse environment for research is designed to work with modern image-guided precision research platforms. Its modular design includes (1) a study workflow manager, (2) a data manager, and (3) a storage manager. The system provides interfaces to, e.g. preclinical treatment planning systems and data analysis plug-ins, and guides the user efficiently through the many steps involved in preclinical research. The system manages various data source locations, and arranges access to the data centrally. Conclusion: A novel preclinical data management system can be designed to improve preclinical workflow, facilitate data exchange between researchers, and support translation to clinical trials. Advances in knowledge: A preclinical data management system such as the one proposed here would greatly benefit preparation, execution and analysis of biological experiments, and will eventually facilitate translation to clinical trials

The heart of Sakurai's Object revealed by ALMA

We present high angular-resolution observations of Sakurai's object using the Atacama Large Millimeter Array, shedding new light on its morpho-kinematical structure. The millimetre continuum emission, observed at an angular resolution of 20 milliarcsec (corresponding to 70 AU), reveals a bright compact central component whose spectral index indicates that it composed of amorphous carbon dust. Based on these findings, we conclude that this emission traces the previously suggested dust disc observed in mid-infrared observations. Therefore, our observations provide the first direct imaging of such a disc. The H$^{12}$CN($J$=4$\rightarrow$3) line emission, observed at an angular resolution of 300 milliarcsec (corresponding to 1000 AU), displays bipolar structure with a north-south velocity gradient. From the position-velocity diagram of this emission we identify the presence of an expanding disc and a bipolar molecular outflow. The inclination of the disc is determined to be $i$=72$^\circ$. The derived values for the de-projected expansion velocity and the radius of the disc are $v_{\rm exp}$=53 km s$^{-1}$ and $R$=277 AU, respectively. On the other hand, the de-projected expansion velocity of the bipolar outflow detected in the H$^{12}$CN($J$=4$\rightarrow$3) emission of approximately 1000 km s$^{-1}$. We propose that the molecular outflow has an hourglass morphology with an opening angle of around 60$^{\circ}$. Our observations unambiguously show that an equatorial disc and bipolar outflows formed in Sakurai's object in less than 30 years after the born-again event occurred, providing important constraints for future modelling efforts of this phenomenon.Comment: 9 pages, 5 figures. Accepted for publication as a Letter in Astronomy and Astrophysic

An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms

Objective: Lung cancer is the deadliest cancer worldwide. To increase treatment potential for lung cancer, pre-clinical models that allow testing and follow up of clinically relevant treatment modalities are essential. Therefore, we developed a single-nodule-based orthotopic non-small cell lung cancer tumor model which can be monitored using multimodal non-invasive imaging to select the optimal image-guided radiation treatment plan. Methods: An orthotopic non-small cell lung cancer model in NMRI-nude mice was established to investigate the complementary information acquired from 80 kVp microcone-beam CT (micro-CBCT) and bioluminescence imaging (BLI) using different angles and filter settings. Different micro-CBCT-based radiation-delivery plans were evaluated based on their dose-volume histogram metrics of tumor and organs at risk to select the optimal treatment plan. Results: H1299 cell suspensions injected directly into the lung render exponentially growing single tumor nodules whose CBCT-based volume quantification strongly correlated with BLI-integrated intensity. Parallel-opposed single angle beam plans through a single lung are preferred for smaller tumors, whereas for larger tumors, plans that spread the radiation dose across healthy tissues are favored. Conclusions: Closely mimicking a clinical setting for lung cancer with highly advanced preclinical radiation treatment planning is possible in mice developing orthotopic lung tumors. Advances in knowledge: BLI and CBCT imaging of orthotopic lung tumors provide complementary information in a temporal manner. The optimal radiotherapy plan is tumor volume-dependent

First Images of the Molecular Gas around a Born-again Star Revealed by ALMA

Born-again stars allow probing stellar evolution in human timescales and provide the most promising path for the formation of hydrogen-deficient post-asymptotic giant branch objects, but their cold and molecular components remain poorly explored. Here we present ALMA observations of V 605 Aql that unveil for the first time the spatio-kinematic distribution of the molecular material associated with a born-again star. Both the continuum and molecular line emission exhibit a clumpy ring-like structure with a total extent of approximate to 1 \u27\u27 in diameter. The bulk of the molecular emission is interpreted as being produced in a radially expanding disk-like structure with an expansion velocity v(exp) similar to 90 km s(-1) and an inclination i approximate to 60 degrees with respect to the line of sight. The observations also reveal a compact high-velocity component, v(exp) similar to 280 km s(-1), that is aligned perpendicularly to the expanding disk. This component is interpreted as a bipolar outflow with a kinematical age tau less than or similar to 20 yr, which could either be material that is currently being ejected from V 605 Aql, or is being dragged from the inner parts of the disk by a stellar wind. The dust mass of the disk is in the range M-dust similar to 0.2-8 x 10(-3) M-circle dot, depending on the dust absorption coefficient. The mass of the CO is MCO approximate to 1.1 x 10(-5) M-circle dot, which is more than three orders of magnitude larger than the mass of the other detected molecules. We estimate a C-12/C-13 ratio of 5.6 +/- 0.6, which is consistent with the single stellar evolution scenario in which the star experienced a very late thermal pulse instead of a nova-like event as previously suggested

A Research Agenda for Hybrid Intelligence:Augmenting Human Intellect With Collaborative, Adaptive, Responsible, and Explainable Artificial Intelligence

We define hybrid intelligence (HI) as the combination of human and machine intelligence, augmenting human intellect and capabilities instead of replacing them and achieving goals that were unreachable by either humans or machines. HI is an important new research focus for artificial intelligence, and we set a research agenda for HI by formulating four challenges

Human cerebrospinal fluid monoclonal CASPR2 autoantibodies induce changes in electrophysiology, functional MRI, and behavior in rodent models

Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a severe autoimmune encephalitis with a variable clinical phenotype including behavioral abnormalities, cognitive decline, epileptic seizures, peripheral nerve hyperexcitability and neuropathic pain. The detailed mechanisms of how CASPR2 autoantibodies lead to synaptic dysfunction and clinical symptoms are largely unknown. Aiming for analyses from the molecular to the clinical level, we isolated antibody-secreting cells from the cerebrospinal fluid of two patients with CASPR2 encephalitis. From these we cloned four anti-CASPR2 human monoclonal autoantibodies (mAbs) with strong binding to brain and peripheral nerves. All were highly hypermutated and mainly of the IgG4 subclass. Mutagenesis studies determined selective binding to the discoidin domain of CASPR2. Surface plasmon resonance revealed affinities with dissociation constants K D in the pico- to nanomolar range. CASPR2 mAbs interrupted the interaction of CASPR2 with its binding partner contactin 2 in vitro and were internalized after binding to CASPR2-expressing cells. Electrophysiological recordings of rat hippocampal slices after stereotactic injection of CASPR2 mAbs showed characteristic afterpotentials following electrical stimulation. In vivo experiments with intracerebroventricular administration of human CASPR2 mAbs into mice and rats showed EEG-recorded brain hyperexcitability but no spontaneous recurrent seizures. Behavioral assessment of infused mice showed a subtle clinical phenotype, mainly affecting sociability. Mouse brain MRI exhibited markedly reduced resting-state functional connectivity without short-term structural changes. Together, the experimental data support the direct pathogenicity of CASPR2 autoantibodies. The minimally invasive EEG and MRI techniques applied here may serve as novel objective, quantifiable tools for improved animal models, in particular for subtle neuropsychiatric phenotypes or repeated measurements